腎移植患者の抗体関連型拒絶反応に対する高用量IVIG療法の有効性および安全性を評価する多施設共同非盲検 第III相試験：結果報告

抄録

【Objective】 Intravenous immunoglobulin (IVIG) has been used to treat antibody-mediated rejection (AMR) ; however, dosage regimens vary across national guidelines. We aimed to evaluate the efficacy of high-dose IVIG (2-4 g/kg) in kidney transplant recipients with AMR.

【Design】 A multicenter, open-label, phase 3 study.

【Methods】 High-dose IVIG therapy (1 g/kg per day, up to four doses) was administered to patients with a pathological diagnosis of active or chronic active AMR, and its efficacy and safety were evaluated six months after treatment initiation. The primary endpoint was renal graft survival six months after IVIG therapy initiation. Secondary endpoints included patient survival six months after initiation, antibody titer over time, percentage of patients with decreased antibody titers, and renal graft function over time. Changes in pathological findings of the renal grafts before and after IVIG administration were evaluated in an exploratory manner. Safety endpoints included adverse events in patients treated with IVIG.

【Results】 Renal graft survival and patient survival at six months were 95.7% [95% confidence interval (CI), 78.1-99.9]. The percentage of patients with decreased HLA antibody titers after IVIG administration was 69.6%. Decreased antibody titers for non-HLA antibodies were observed after IVIG administration. Renal graft function was stable throughout the study period, regardless of AMR type. Post- IVIG histopathological evaluation was performed in 13 (56.5%) of 23 patients, of whom eight showed histopathological improvement in AMR with reduced microvascular inflammation scores after IVIG administration. Adverse reactions were noted in 16 (64.0%) of 25 patients who underwent the treatment protocol; however, all were transient.

【Conclusions】 These results suggest that high-dose IVIG (1 g/kg/day, up to four doses) is a promising treatment for AMR.